The present invention relates to novel crosslinkable copolymers, to a process for the preparation thereof and to the use thereof for the manufacture of mouldings, especially ophthalmic mouldings.
U.S. Pat. Nos. 5,760,100 or 5,807,944 disclose crosslinkable amphiphilic block copolymers comprising a hydrophobic middle block to which are linked two or more hydrophilic blocks. While the materials disclosed therein in general have proven to be effective as bulk material for the manufacture of biomedical articles, the availability, chemical constitution and size of suitable hydrophilic blocks as well as the further processing of the known block copolymers is often problematic. In particular, the control of the segmental length of the hydrophilic segments is often difficult. Therefore, it would be highly desirable to provide more easily accessible hydrophilic blocks of variable chain length having a single functional group undergoing coupling with the hydrophobic segment and one or more different functional groups useful to attach a polymerizable moiety. Such hydrophilic blocks would allow to design specific crosslinkable amphiphilic block copolymers with specific polymer and segmental architectures depending on the desired use. In addition, a simplified manufacture of mouldings from such amphiphilic block copolymers would be desirable which omits time consuming steps such as, for example, the removal of extractables, that are unpolymerized components or compounds that are not firmly anchored in the polymer network, after the polymerization or crosslinking step.
Therefore, it is an object of the invention to provide novel crosslinkable amphiphilic block copolymers, within the application also called prepolymers, which are based on easily accessible hydrophilic blocks with high variability of chemical constitution and segmenral length, and which make it possible to manufacture mouldings, in particular biomedical mouldings such as especially ophthalmic mouldings, in a very efficient manner.
The present invention therefore in one aspect relates to a crosslinkable amphiphilic block copolymer of formula 
wherein A is a hydrophobic segment selected from the group consisting of a polysiloxane, a perfluoroalkyl polyether and mixtures thereof,
L is is a bivalent linking group of formula
xe2x80x94X1xe2x80x94C(O)xe2x80x94NHxe2x80x94Rxe2x80x94NHxe2x80x94C(O)xe2x80x94X2xe2x80x94xe2x80x83xe2x80x83(2a),
xe2x80x94X1xe2x80x94C(O)xe2x80x94Rxe2x80x94C(O)xe2x80x94X2xe2x80x94xe2x80x83xe2x80x83(2b),
xe2x80x94C(O)xe2x80x94X2xe2x80x94xe2x80x83xe2x80x83(2c),
xe2x80x94X1xe2x80x94C(O)xe2x80x94xe2x80x83xe2x80x83(2d) 
or
xe2x80x94X1xe2x80x94C(O)xe2x80x94X2xe2x80x94xe2x80x83xe2x80x83(2e),
wherein X1 and X2 are each independently of the other a group xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94 or xe2x80x94NR1xe2x80x94, R1 is hydrogen or C1-C4-alkyl, R is linear or branched C1-C18-alkylene or unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted C6-C10-arylene, C7-C18-aralkylene, C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene, C3-C8-cycloalkylene, C3-C8-cycloalkylene-C1-C6-alkylene, C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C1-C6-alkylene-C3-C8-cycloalkylene-C1-C6-alkylene; (alk) is C2-C12-alkylene;
(oligomer) is the radical of a hydrophilic telomer which is derived from one or more different copolymerizable vinyl monomers;
Q is an organic radical comprising at least one crosslinkable or polymerizable group;
m is an integer from 1 to 4, and n is an integer xe2x89xa71.
According to one preferred embodiment of the invention, the segment A comprises a polysiloxane block having terminal alkylene groups of formula 
in which (alkxe2x80x2) is alkylene having up to 20 carbon atoms which may be interrupted by xe2x80x94Oxe2x80x94; 80-100% of the radicals R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2 and R3xe2x80x3, independently of one another, are C1-C8-alkyl and 0-20% of the radicals R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2 and R3xe2x80x3, independently of one another, are C3-C12-alkenyl, unsubsttituted or C1-C4 alkyl- or C1-C4- alkoxy-substituted phenyl, fluoro(C1-C18-alkyl) or cyano(C1-C12-alkyl), x is 0 or 1, d1 is an integer of from 5 to 700, d2 is (nxe2x88x922) if x is 0, and is n if x is 1 wherein n is as defined above, and the sum of (d1+d2) is from 5 to 700.
In a preferred meaning, the sum of (d1+d2) is an integer from 10 to 500, more preferably 10 to 300, particularly preferably 20 to 200 and in particular 25 to 150.
(alkxe2x80x2) is preferably C2-C8-alkylene, which may be interrupted by -O- and more preferably C2-C6-alkylene which may be interrupted by xe2x80x94Oxe2x80x94. Examples of particular preferred radicals (alkxe2x80x2) are linear or branched C2-C6 alkylene or a radical xe2x80x94(CH2)1-3xe2x80x94Oxe2x80x94(CH2)1-3xe2x80x94, especially C2-C4-alkylene or a radical xe2x80x94(CH2)2-3xe2x80x94Oxe2x80x94(CH2)2-3xe2x80x94.
Preferably the radicals R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2 and R3xe2x80x3 are each independently of one another C1-C6-alkyl, more preferably each C1-C4-alkyl, more preferably each C1-C2-alkyl and in particular each methyl.
One embodiment of suitable polysiloxane hydrophobic blocks (A) emcompasses a radical of the above formula (3), wherein x is 0, d2 is 0, d1 is an integer from 5 to 700, preferably 10 to 500, more preferably 10 to 300, even more preferably 20 to 200 and in particular preferably 25 to 150, R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2 and R3xe2x80x3 are each independently of one another C1-C6-alkyl, and for (alkxe2x80x2) the above given meanings and preferences apply.
Another embodiment of suitable polysiloxane hydrophobic blocks (A) emcompasses a radical of the above formula (3), wherein x is 0, d2 is the sum of (nxe2x88x922) and is xe2x89xa71, and for R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2 and R3xe2x80x3,d1 and (alkxe2x80x2) the above-given meanings and preferences each apply.
Still another embodiment of suitable polysiloxane hydrophobic blocks (A) emcompasses a radical of the above formula (3), wherein x is 1, d2 is equivalent to n, and for R2, R2xe2x80x2, R2xe2x80x3, R2xe2x80x2xe2x80x3, R2*, R3, R3xe2x80x2, d1 and R3xe2x80x3 each the above-given meanings and preferences each apply.
According to another embodiment of the invention, the oxygen-permeable polymer in segment A comprises a perfluoroalkyl-polyether block of formula
xe2x80x94(E)kxe2x80x94Zxe2x80x94CF2xe2x80x94(OCF2)b1xe2x80x94(OCF2CF2)b2xe2x80x94OCF2xe2x80x94Zxe2x80x94(E)kxe2x80x83xe2x80x83(4)
in which (b1+b2) is a number in the range from 10 to 100; each Z, independently of the others, is a divalent radical having up to 12 carbon atoms or a bond; each E, independently of the others, is alkoxy, e.g. xe2x80x94(OCH2CH2)axe2x80x94, where a has a value of from 0 to 2 as a statistical average, and where the link xe2x80x94Zxe2x80x94Exe2x80x94 represents the sequence xe2x80x94Zxe2x80x94(OCH2CH2)axe2x80x94; and k is 0 or 1.
Z is preferably a bond, C1-C8-alkylene or xe2x80x94CONH-phenylene, in which the xe2x80x94COxe2x80x94 moiety is linked to a CF2 group. Z is particularly preferably C1-C4-alkylene, in particular methylene.
The perfluoroalkoxy units OCF2 and OCF2CF2 having the indices b1 and b2 in Formula (4) can have a random distribution. The sum of the indices (b1+b2) is preferably a number in the range from 10 to 50, particularly preferably from 10 to 30. The ratio b1:b2 is preferably in the range from 0.5 to 1.5, in particular in the range from 0.8 to 1.2.
In one embodiment of the invention, the segment A may comprise one of the polymers illustrated above, in particular a polysiloxane. According to another embodiment, the polymer in segment A may comprise more than one kind of polymers as illustrated above, e.g., may comprise perfluoroalkylene polyether subsegments and polysiloxane subsegments.
Segments A of the prepolymers of the invention have a mean molecular weight of for example in the range from about 1,000 to about 50,000, preferably in the range from about 1,500 to about 30000 and particularly preferably in the range from about 2,000 to about 20,000.
The linking groups L of formulae (2a)-(2e) are to be understood that the left bond is directed to A and the right bond is directed to (alk).
If X1 or X2 is a group xe2x80x94NR1xe2x80x94, R1 is preferably methyl, ethyl or in particular hydrogen. X1 and X2 are each independently of the other preferably a group xe2x80x94Oxe2x80x94 or xe2x80x94NR1xe2x80x94 and more preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94.
R as alkylene in formula (2b) is preferably linear or branched C1-C12-alkylene, more preferably C1-C6-alkylene and most preferably C1-C4-alkylene.
R as alkylene in formula (2a) is preferably a linear or branched C3-C14alkylene radical, more preferably a linear or branched C4-C12alkylene radical and most preferably a linear or branched C6-C10alkylene radical.
When R is arylene, it is, for example, naphthylene or especially phenylene, each of which may be substituted, for example, by C1-C4-alkyl or by C1-C4-alkoxy. Preferably, R as arylene is 1,3- or 1,4-phenylene that is unsubstituted or substituted by C1-C4-alkyl or by C1-C4-alkoxy in the ortho-position to at least one linkage site.
R as aralkylene is preferably naphthylalkylene and most preferably phenylalkylene. The alkylene group in aralkylene contains preferably from 1 to 12, more preferably from 1 to 6 and most preferably from 1 to 4 carbon atoms. Most preferably, the alkylene group in aralkylene is methylene or ethylene.
When R is cycloalkylene, it is preferably C5-C6cycloalkylene and most preferably cyclohexylene that is unsubstituted or substituted by methyl.
When R is cycloalkylene-alkylene, it is preferably cyclopentylene-C1-C4-alkylene and especially cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group cycloalkylene-alkylene is cyclohexylene-ethylene and, most preferably, cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups.
When R is alkylene-cycloalkylene-alkylene, it is preferably C1-C4-alkylene-cyclopentylene-C1-C4-alkylene and especially C1-C4-alkylene-cyclohexylene-C1-C4-alkylene, each unsubstituted or mono- or poly-substituted by C1-C4-alkyl, especially methyl. More preferably, the group alkylene-cycloalkylene-alkylene is ethylene-cyclohexylene-ethylene and, most preferably, is methylene-cyclohexylene-methylene, each unsubstituted or substituted in the cyclohexylene radical by from 1 to 3 methyl groups.
R as C3-C8-cycloalkylene-C1-C2-alkylene-C3-C8-cycloalkylene or C6-C10-arylene-C1-C2-alkylene-C6-C10-arylene is preferably C5-C6-cycloalkylene-methylene-C5-C6-cycloalkylene or phenylene-methylene-phenylene, each of which may be unsubstituted or substituted in the cycloalkyl or phenyl ring by one or more methyl groups.
The radical R in formula (2a) has a symmetrical or, preferably, an asymmetrical structure.
L is preferably a radical of formula (2a). An especially preferred group of linking groups L comprises those of formula (2a), wherein R is linear or branched C6-C10alkylene; or cyclohexylene-methylene or cyclohexylene-methylene-cyclohexylene each unsubstituted or substituted in the cyclohexyl moiety by from 1 to 3 methyl groups.
Most preferably the bivalent radical R in formula (2a) is derived from a diisocyanate and in particular from a diisocyanate selected from the group isophorone diisocyanate (IPDI), 4,4xe2x80x2-methylenebis (cyclohexyl isocyanate), 1,6-diisocyanato-2,2,4-trimethyl-n-hexane (TMDI), methylenebis(cyclohexyl-4-isocyanate) and hexamethylene diisocyanate (HMDI).
Further suitable linking groups L comprise, for example, xe2x80x94C(O)Oxe2x80x94, xe2x80x94OC(O)xe2x80x94, xe2x80x94C(O)NHxe2x80x94 or xe2x80x94NHC(O)xe2x80x94.
The variable (alk) is preferably C2-C8-alkylene, more preferably C2-C6-alkylene, even more preferably C2-C4-alkylene and particularly preferably 1,2-ethylene. The alkylene radical (alk) may be branched or preferably linear.
The variable m is, for example, a number from 1 to 4, preferably from 1 to 3 and especially from 1 to 2.
The telomer radical (oligomer)-(Q)m corresponds, for example, to formula 
wherein B and Bxe2x80x2 are each independently of the other a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer that is substituted by a hydrophilic substituent by replacing the vinylic double bond by a single bond,
Bxe2x80x3 is a 1,2-ethylene radical derivable from a copolymerizable vinyl monomer by replacing the vinylic double bond by a single bond,
Q is an organic radical comprising at least one crosslinkable or polymerizable group;
p and q are each independently of another an integer from 0 to 150, wherein the total of (p+q) is an integer from 2 to 150,
u is, for example, an integer from 1 to 4, and
T is a monovalent group that is suitable to act as a polymerization chain-reaction terminator.
T is, for example, hydrogen.
Suitable hydrophilic substituents of the radicals B or Bxe2x80x2 may be non-ionic, anionic, cationic or zwitterionic substituents. Accordingly, the telomer chain of formula (5) may be a charged chain containing anionic, cationic and/or zwitterionic groups or may be an uncharged chain. In addition, the telomer chain may comprise a copolymeric mixture of uncharged and charged units. The distribution of the charges within the telomer, if present, may be random or blockwise.
In one preferrred embodiment of the invention, the telomer radical of formula (5) is composed solely of non-ionic monomer units B and optionally Bxe2x80x2.
Suitable non-ionic substituents of B or Bxe2x80x2 include for example a radical C1-C6-alkyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94OH, C1-C4-alkoxy and xe2x80x94NR4R4xe2x80x2, wherein R4 and R4xe2x80x2 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl; phenyl which is substituted by hydroxy, C1-C4-alkoxy or xe2x80x94NR4R4xe2x80x2, wherein R4 and R4xe2x80x2 are as defined above; a radical xe2x80x94COOY, wherein Y is C1-C24-alkyl which is unsubstituted or substituted, for example, by hydroxy, C1-C4-alkoxy, xe2x80x94Oxe2x80x94Si(CH3)3, xe2x80x94NR4R4xe2x80x2 wherein R4 and R4xe2x80x2 are as defined above, a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94R9 wherein R9 is hydrogen or C1-C6-alkyl, or a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide with 1 to 8 sugar units or is a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94R9, wherein R9 is as defined above, or Y is C5-C8-cycloalkyl which is unsubstituted or substituted by C1-C4-alkyl or C1-C4-alkoxy, or is unsubstituted or C1-C4-alkyl- or C1-C4-alkoxy-substituted phenyl or C7-C12-aralkyl; xe2x80x94CONY1Y2 wherein Y1 and Y2 are each independently hydrogen, C1-C12-alkyl, which is unsubstituted or substituted for example by hydroxy, C1-C4-alkoxy or a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94R9 wherein R9 is as defined above, or Y1 and Y2 together with the adjacent N-atom form a five- or six-membered heterocyclic ring having no additional heteroatom or one additional oxygen or nitrogen atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen; or C1-C12-alkyl which is unsubstituted or substituted by xe2x80x94NR4R4xe2x80x2; or is a radical xe2x80x94C(O)xe2x80x94C1-C4-alkyl; and wherein R4 and R4xe2x80x2 are as defined above; or a five- to seven-membered heterocyclic radical having at least one N-atom and being bound in each case via said nitrogen atom.
Suitable anionic substituents of B or Bxe2x80x2 include for example C1-C6-alkyl which is substituted by xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 and xe2x80x94COOH; phenyl which is substituted by one or more same or different substituents selected from the group consisting of xe2x80x94SO3H, xe2x80x94COOH, xe2x80x94OH and xe2x80x94CH2xe2x80x94SO3H; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C1-C24-alkyl which is substituted for example by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2 or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of an anionic carbohydrate; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C24-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, or xe2x80x94OPO3H2 and Y6 independently has the meaning of Y5 or is hydrogen or C1-C12-alkyl; or xe2x80x94SO3H; each in form of the free acid or in form of a salt, for example a sodium, potassium, ammonium or the like salt thereof.
Suitable cationic substituents of B or Bxe2x80x2 include C1-C12-alkyl which is substituted by a radical xe2x80x94NR4R4xe2x80x2R4xe2x80x3+Anxe2x88x92, wherein R4, R4xe2x80x2 and R4xe2x80x3 are each independently of another hydrogen or unsubstituted or hydroxy-substituted C1-C6-alkyl or phenyl, and Anxe2x88x92 is an anion, for example a biomedical acceptable anion such as a halide; or a radical xe2x80x94C(O)OY7, wherein Y7 is C1-C24-alkyl which is substituted by xe2x80x94NR4R4xe2x80x2R4xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted for example by hydroxy, wherein R4, R4xe2x80x2, R4xe2x80x3 and Anxe2x88x92 are as defined above.
Suitable zwitterionic substituents of B or Bxe2x80x2 include a radical -R10xe2x80x94Zw, wherein R10 is a direct bond or a functional group, for example a carbonyl, carbonate, amide, ester, dicarboanhydride, dicarboimide, urea or urethane group; and Zw is an aliphatic moiety comprising one anionic and one cationic group each.
The following preferences apply to the hydrophilic substituents of B and Bxe2x80x2:
(i) non-ionic substituents:
Preferred alkyl substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR4R4xe2x80x2, wherein R4 and R4xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl, preferably hydrogen, methyl or ethyl and particularly preferably hydrogen or methyl, for example xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94N(CH3)2.
Preferred phenyl substituents of B or Bxe2x80x2 are phenyl which is substituted by xe2x80x94NH2 or N(C1-C2-alkyl)2, for example o-, m- or p-aminophenyl.
In case that the hydrophilic substituent of B or Bxe2x80x2 is a radical xe2x80x94COOY, Y as optionally substituted alkyl is preferably C1-C6-alkyl, more preferably C1-C4-alkyl, even more preferably C1-C3-alkyl and particularly preferably methyl or ethyl, each of which being unsubstituted or substituted as mentioned above. In case that the alkyl radical Y is substituted by xe2x80x94NR4R4xe2x80x2, the above-given meanings and preferences apply for R4 and R4xe2x80x2. Examples of suitable saccharide substituents xe2x80x94Oxe2x80x94G of the alkyl radical Y that is substituted by xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G are the radical of a mono- or disaccharide, for example glucose, acetyl glucose, methyl glucose, glucosamine, N-acetyl glucosamine, glucono lactone, mannose, galactose, galactosamine, N-acetyl galactosamine, fructose, maltose, lactose, fucose, saccharose or trehalose, the radical of an anhydrosaccharide such as levoglucosan, the radical of a glucosid such as octylglucosid, the radical of a sugar alcohol such as sorbitol, the radical of a sugar acid derivative such as lactobionic acid amide, or the radical of an oligosaccharide with a maximum of 8 sugar units, for example fragments of a cyclodextrin, starch, chitosan, maltotriose or maltohexaose. The radical xe2x80x94Oxe2x80x94G preferably denotes the radical of a mono- or disaccharide or the radical of a cyclodextrin fragment with a maximum of 8 sugar units. Particular preferred saccharide radicals xe2x80x94Oxe2x80x94G are the radical of trehalose or the radical of a cyclodextrin fragment. In case that the alkyl radical Y is substituted by a radical xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94R9 or xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is xe2x80x94Oxe2x80x94(CH2CH2O)1-24xe2x80x94R9, the number of (CH2CH2O) units is preferably from 1 to 12 in each case and more preferably from 2 to 8. R9 is preferably C1-C2-alkyl or in particular hydrogen. Y as C5-C8-cycloalkyl is for example cyclopentyl or preferably cyclohexyl, each of which being unsubstituted or substituted for example by 1 to 3 C1-C2-alkyl groups. Y as C7-C12-aralkyl is for example benzyl.
Preferred nonionic radicals xe2x80x94COOY are those wherein Y is C1-C3-alkyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of hydroxy;; C1-C2-alkoxy; xe2x80x94Oxe2x80x94Si(CH3)3; and xe2x80x94NR4R4xe2x80x2 wherein R4 and R4xe2x80x2 are each independently of another hydrogen or C1-C4-alkyl; or Y is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12xe2x80x94H; or is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G, wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
More preferred non-ionic radicals xe2x80x94COOY are those wherein Y is C1-C2-alkyl; or C2-C4-alkyl which is substituted by one or two substituents selected from the group consisting of xe2x80x94OH and xe2x80x94NR4R4xe2x80x2 wherein R4 and R4xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl; or a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-12xe2x80x94H; or is a radical xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide.
Particularly preferred radicals xe2x80x94COOY comprise those wherein Y is C1-C2-alkyl, particularly methyl; or C2-C3-alkyl, which is unsubstituted or substituted by hydroxy or N,N-di-C1-C2-alkylamino, or is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)1-3xe2x80x94H or xe2x80x94C2-C3-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose or the radical of a cyclodextrin fragment with a maximum of 8 sugar units.
Preferred non-ionic substituents xe2x80x94C(O)xe2x80x94NY1Y2 of B or Bxe2x80x2 are those wherein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom. Even more preferred meanings of Y1 and Y2, independently of each other, are hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy; or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring. Particularly preferred non-ionic radicals xe2x80x94C(O)xe2x80x94NY1Y2 are those wherein Y1 and Y2 are each independently of the other hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl; or Y1 and Y2 together with the adjacent N-atom form a morpholino ring.
Preferred non-ionic substituents xe2x80x94OY3 of B or Bxe2x80x2 are those wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl. Y3 is particularly preferred hydrogen or acetyl.
Preferred non-ionic heterocyclic substituents of B or Bxe2x80x2 are a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N- or O- heteroatom, or is a 5 to 7-membered lactame. Examples of such heterocyclic radicals are N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methyl pyridin-5-yl, 2-, 3-oder 4-hydroxypyridinyl, N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl or 4-N-methylpiperazin-1-yl, particularly N-morpholinyl or N-pyrrolidonyl.
A group of preferred non-ionic substituents of B or Bxe2x80x2 comprises C1-C2-alkyl, which is substituted by xe2x80x94OH or xe2x80x94NR4R4xe2x80x2, wherein R4 and R4xe2x80x2 are each independently of the other hydrogen or C1-C2-alkyl; a radical xe2x80x94COOY wherein Y is C1-C3-alkyl; C2-C4-alkyl which is substituted by xe2x80x94OH, xe2x80x94NR4R4xe2x80x2 wherein R4 and R4xe2x80x2 are each independently of another hydrogen or C1-C2-alkyl, or Y is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)2-8xe2x80x94H or xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of a saccharide; a radical xe2x80x94C(O)xe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C6-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a heterocyclic 6-membered ring having no further heteroatom or having one further N- or O-atom; a radical xe2x80x94OY3, wherein Y3 is hydrogen, C1-C4-alkyl which is unsubstituted or substituted by xe2x80x94NH2 or xe2x80x94N(C1-C2-alkyl)2, or is a group xe2x80x94C(O)C1-C2-alkyl; or a 5- or 6-membered heteroaromatic or heteroaliphatic radical having one N-atom and in addition no further heteroatom or an additional N-, O- or S-heteroatom, or a 5 to 7-membered lactame.
A group of more preferred non-ionic substituents of B or Bxe2x80x2 comprises a radical xe2x80x94COOY, wherein Y is C1-C2-alkyl, C2-C3-alkyl, which is substituted by hydroxy, amino or N,N-di-C1-C2-alkylamino, or is a radical xe2x80x94CH2CH2xe2x80x94Oxe2x80x94(CH2CH2O)2-8xe2x80x94H or xe2x80x94C2-C4-alkylene-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose or a cyclodextrin fragment with a maximum of 8 sugar units; a radical xe2x80x94COxe2x80x94NY1Y2, wherein Y1 and Y2 are each independently of the other hydrogen or C1-C4-alkyl which is unsubstituted or substituted by hydroxy, or Y1 and Y2 together with the adjacent N-atom form a Nxe2x80x94C1-C2-alkylpiperazino or morpholino ring; or a heterocyclic radical selected from the group consisting of N-pyrrolidonyl, 2- or 4-pyridinyl, 2-methylpyridin-5-yl, 2-, 3- oder 4-hydroxypyridinyl, N-xcex5-caprolactamyl, N-imidazolyl, 2-methylimidazol-1-yl, N-morpholinyl and 4-N-methylpiperazin-1-yl.
A particularly preferred group of non-ionic substituents of B or Bxe2x80x2 comprises the radicals xe2x80x94COOxe2x80x94C1-C2-alkyl, xe2x80x94COOxe2x80x94(CH2)2-3xe2x80x94OH, xe2x80x94CONH2, xe2x80x94CON(CH3)2, xe2x80x94CONHxe2x80x94(CH2)2xe2x80x94OH, 
xe2x80x94COO(CH2)2-4xe2x80x94NHC(O)xe2x80x94Oxe2x80x94G wherein xe2x80x94Oxe2x80x94G is the radical of trehalose or a cyclodextrin fragment with a maximum of 8 sugar units. Particularly preferred non-ionic substituents of B and Bxe2x80x2 are xe2x80x94CONH2, xe2x80x94CON(CH3)2 or 
(ii) anionic substituents:
Preferred anionic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is substituted by one or more substituents selected from the group consisting of xe2x80x94SO3H and xe2x80x94OPO3H2, for example xe2x80x94CH2xe2x80x94SO3H; phenyl which is substituted by xe2x80x94SO3H or sulfomethyl, for example o-, m- or p-sulfophenyl or o-, m- or p-sulfomethylphenyl; xe2x80x94COOH; a radical xe2x80x94COOY4, wherein Y4 is C2-C6-alkyl which is substituted by xe2x80x94COOH, xe2x80x94SO3H, xe2x80x94OSO3H, xe2x80x94OPO3H2, or by a radical xe2x80x94NHxe2x80x94C(O)xe2x80x94Oxe2x80x94Gxe2x80x2 wherein Gxe2x80x2 is the radical of lactobionic acid, hyaluronic acid or sialic acid, in particular C2-C4-alkyl which is substituted by xe2x80x94SO3H or xe2x80x94OSO3H; a radical xe2x80x94CONY5Y6 wherein Y5 is C1-C6-alkyl substituted by sulfo, in particular C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, for example the radical xe2x80x94C(O)xe2x80x94NHxe2x80x94C(CH3)2xe2x80x94CH2xe2x80x94SO3H; or xe2x80x94SO3H; or a suitable salt thereof. Particular preferred anionic substituents of B or Bxe2x80x2 are xe2x80x94COOH, xe2x80x94SO3H, o-, m- or p-sulfophenyl, o-, m- or p-sulfomethylphenyl, a radical xe2x80x94CONY5Y6 wherein Y5 is C2-C4-alkyl substituted by sulfo, and Y6 is hydrogen, or a biomedical acceptable salt thereof, for example a sodium or ammonium salt.
(iii) cationic substituents:
Preferred cationic substituents of B or Bxe2x80x2 are C1-C4-alkyl, in particular C1-C2-alkyl, which is in each case substituted by xe2x80x94NR9R9xe2x80x2R9xe2x80x3+Anxe2x88x92; or a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C6-alkyl, in particular C2-C4-alkyl, which is in each case substituted by xe2x80x94NR4R4xe2x80x2R4xe2x80x3+Anxe2x88x92 and is further unsubstituted or substituted by hydroxy. R4, R4xe2x80x2 and R4xe2x80x3 are each independently of another preferably hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. Examples of suitable anions Anxe2x88x92 are Halxe2x88x92, wherein Hal is halogen, for example Brxe2x88x92, Fxe2x88x92, Jxe2x88x92 or particularly Clxe2x88x92, furthermore HCO3xe2x88x92, CO32xe2x88x92, H2PO3xe2x88x92, HPO32xe2x88x92, PO33xe2x88x92, HSO4xe2x88x92, SO42xe2x88x92 or the radical of an organic acid such as OCOCH3xe2x88x92 and the like. A particularly preferred cationic substituent of B or Bxe2x80x2 is a radical xe2x80x94C(O)OY7 wherein Y7 is C2-C4-alkyl, which is substituted by xe2x80x94N(C1-C2-alkyl)3+Anxe2x88x92 and is further substituted by hydroxy, and Anxe2x88x92 is an anion, for example the radical xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OH)xe2x80x94CH2xe2x80x94N(CH3)3+Anxe2x88x92.
(iv) zwitterionic substituents xe2x80x94R10xe2x80x94Zw:
R10 is a preferably a carbonyl, ester or amide functional group and more preferably an ester group xe2x80x94C(O)xe2x80x94Oxe2x80x94.
Suitable anionic groups of the moiety Zw are for example xe2x80x94COOxe2x88x92, xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92, xe2x80x94OPO3Hxe2x88x92 or bivalent xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94 or xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94Oxe2x80x94, preferably a group xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 or a bivalent group xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94, and in particular a group xe2x80x94SO3xe2x88x92.
Suitable cationic groups of the moiety Zw are for example a group xe2x80x94NR4R4xe2x80x2R4xe2x80x3+ or a bivalent group xe2x80x94NR4R4xe2x80x2+xe2x80x94, wherein R4, R4xe2x80x2 and R4xe2x80x3 are as defined above, and are each independently of the other, preferably hydrogen or C1-C6-alkyl, preferably hydrogen or C1-C4-alkyl and most preferably each methyl or ethyl.
The moiety Zw is for example C2-C30-alkyl, preferably C2-C12-alkyl, and more preferably C3-C8-alkyl, which is in each case uninterrupted or interrupted by xe2x80x94Oxe2x80x94 and substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and, in addition, is further unsubstituted or substituted by a radical xe2x80x94OY8, wherein Y8 is hydrogen or the acyl radical of a carboxylic acid.
Y8 is preferably hydrogen or the acyl radical of a higher fatty acid.
Zw is preferably C2-C12-alkyl and even more preferably C3-C8-alkyl which is substituted or interrupted by one of the above-mentioned anionic and cationic groups each, and in addition may be further substituted by a radical xe2x80x94OY8.
A preferred group of zwitter-ionic substituents xe2x80x94R3xe2x80x94Z corresponds to the formula
xe2x80x94C(O)O-(alkxe2x80x2xe2x80x3)-N(R4)2+-(alk*)-Anxe2x88x92
or
xe2x80x94C(O)O-(alkxe2x80x3)-Oxe2x80x94PO2xe2x88x92xe2x80x94(O)0-1-(alkxe2x80x2xe2x80x3)-N(R4)3+
wherein R9 is hydrogen or C1-C6-alkyl; Anxe2x88x92 is an anionic group xe2x80x94COO31 , xe2x80x94SO3xe2x88x92, xe2x80x94OSO3xe2x88x92 or xe2x80x94OPO3Hxe2x88x92, preferably xe2x80x94COOxe2x88x92 or xe2x80x94SO3xe2x88x92 and most preferably xe2x80x94SO3xe2x88x92, alk* is C1-C12-alkylene, (alkxe2x80x3) is C2-C24-alkylene which is unsubstituted or substituted by a radical xe2x80x94OY8, Y8 is hydrogen or the acyl radical of a carboxylic acid, and (alkxe2x80x2xe2x80x3) is C2-C8-alkylene.
(alk*) is preferably C2-C8-alkylene, more preferably C2-C6-alkylene and most preferably C2-C4-alkylene. (alkxe2x80x3) is preferably C2-C12-alkylene, more preferably C2-C6-alkylene and particularly preferably C2-C3-alkylene which is in each case unsubstituted or substituted by hydroxy or by a radical xe2x80x94OY8. (alkxe2x80x2xe2x80x3) is preferably C2-C4-alkylene and more preferably C2-C3-alkylene. R9 is hydrogen or C1-C4-alkyl, more preferably methyl or ethyl and particularly preferably methyl. A preferred zwitterionic substituent of B or Bxe2x80x2 is of formula
xe2x80x94C(O)Oxe2x80x94CH2xe2x80x94CH(OY8)xe2x80x94CH2xe2x80x94Oxe2x80x94PO2xe2x88x92xe2x80x94(CH2)2xe2x80x94N(CH3)3+,
wherein Y8 is hydrogen or the acyl radical of a higher fatty acid.
B denotes for example a radical of formula 
preferably a radical of formula (6a), wherein R5 is hydrogen or C1-C4-alkyl, preferably hydrogen or methyl; R6 is a hydrophilic substituent, wherein the above given meanings and preferences apply; R7 is C1-C4-alkyl, phenyl or a radical xe2x80x94C(O)OY9, wherein Yg is hydrogen or unsubstituted or hydroxy-substituted C1-C4-alkyl; and R8 is a radical xe2x80x94C(O)Y9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9xe2x80x2 independently has the meaning of Y9.
R7 is preferably C1-C2-alkyl, phenyl or a group xe2x80x94C(O)OY9. R8 is preferably a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each independently of the other hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl. Particularly preferred xe2x80x94CHR7-CHR8xe2x80x94 units according to the invention are those wherein R7 is methyl or a group xe2x80x94C(O)OY9 and R8 is a group xe2x80x94C(O)OY9xe2x80x2 or xe2x80x94CH2xe2x80x94C(O)OY9xe2x80x2 wherein Y9 and Y9xe2x80x2 are each hydrogen, C1-C2-alkyl or hydroxy-C1-C2-alkyl.
Bxe2x80x2 independently may have one of the meanings given above for B.
The crosslinkable or polymerizable group contained in Q is preferably an ethylenically unsaturated Cxe2x80x94C double bond. A suitable substituent Q of the radical (oligomer) or Bxe2x80x3 is, for example, a radical of the formula
xe2x80x94(R11)txe2x80x94Xxe2x80x94Q1xe2x80x83xe2x80x83(7),
wherein R11 is C1-C8-alkylene or a radical of formula
xe2x80x94C(O)xe2x80x94X3-Alk-xe2x80x83xe2x80x83(8a),
xe2x80x94C(O)xe2x80x94O-Alkxe2x80x2-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94(CH2CH2O)gxe2x80x94CH2CH2xe2x80x94,xe2x80x83xe2x80x83(8b)
or
xe2x80x94C(O)xe2x80x94O-Alkxe2x80x2-NHxe2x80x94C(O)xe2x80x94Oxe2x80x94G1xe2x80x94xe2x80x83xe2x80x83(8c),
Alk is C2-C12-alkylene which is unsubstituted or substituted, for example, by hydroxy or a radical xe2x80x94N(R12)3+Anxe2x80x94 wherein R12 is hydrogen or C1-C4-alkyl and Anxe2x88x92 is an anion, Alkxe2x80x2 is C2-C12-alkylene, X3 is xe2x80x94Oxe2x80x94 or xe2x80x94NR13xe2x80x94, R13 is hydrogen or C1-C4-alkyl, t is an integer of 0 or 1, g is an integer from 1 to 23, G1 independently has the meaning of the saccharide radical G reduced by one hydroxy group; X is a group xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NR13xe2x80x2xe2x80x94 or xe2x80x94N(R13xe2x80x2)2+xe2x80x94Anxe2x88x92 wherein R13xe2x80x2 is hydrogen or C1-C4-alkyl and Anxe2x88x92 is an anion, Q1 is, for example, a radical R14 as defined below or is a radical of formula 
(Alkxe2x80x3) is linear or branched C3-C6-alkylene, (Alk*) is linear or branched C1-C6-alkylene, (Alk**) is linear or branched C2-C12-alkylene, and
R14 is, for example, a radical of formula 
wherein R17 is hydrogen, C1-C4-alkyl or halogen, and each of R15 and R16 independently of the other is hydrogen, C1-C4-alkyl, phenyl, carboxy or halogen.
R11 as alkylene is preferably methylene. If R11 is a radical of formula (8a), (Alk) is preferably C2-C6-alkylene, more preferably C2-C4-alkylene and in particular ethylene; and X3 is preferably xe2x80x94NHxe2x80x94, xe2x80x94N(C1-C2-alkyl)- or xe2x80x94Oxe2x80x94, in particular xe2x80x94NHxe2x80x94 or xe2x80x94N(C1-C2-alkyl)-. If R11 is a radical of formula (8b), (Alkxe2x80x2) is preferably C2-C6-alkylene, more preferably C2-C4-alkylene and in particular ethylene; and g is preferably an integer of from 1 to 12 and especially from 2 to 8. If R11 is a radical of formula (8c), for (Alkxe2x80x2) the above given preferences apply; and xe2x80x94OG1 is preferably the radical of trehalose or a cyclodextrin fragment with a maximum of 8 sugar units each reduced by one hydroxy group.
R11 is preferably a radical of formula (8a). The variable t is preferably the number 1. X is preferably xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94, in particular xe2x80x94Oxe2x80x94.
R17 is preferably hydrogen, methyl or chlorine and most preferably hydrogen or methyl. Each of R15 and R16 independently of the other is preferably hydrogen, carboxy, chlorine, methyl or phenyl. In a preferred embodiment of the invention, R15 is hydrogen or methyl and R16 is hydrogen or carboxy. Most preferably, R15 and R16 are each hydrogen.
Examples of suitable radicals R14 are vinylcarbonyl, 1-methylvinylcarbonyl, styrylcarbonyl, 2-carboxyvinylcarbonyl, 2-chloro-2-carboxyvinylcarbonyl, 1,2-dichloro-2-carboxyvinylcarbonyl, 1,2-dimethyl-2-carboxyvinylcarbonyl and 2-methyl-2-carboxyvinylcarbonyl.
Especially preferred radicals R14 correspond to formula (10) wherein R17 is hydrogen or methyl, R15 is carboxy or particularly hydrogen, and R16 is hydrogen, methyl, chlorine or phenyl, in particular hydrogen.
The radical -[(Alkxe2x80x3)-OH]xe2x80x94 in formula (9a) is preferably 2-hydroxy-1,3-propylene. (Alk*) is preferably C1-C3-alkylene, for example methylene or in particular 1,1-dimethylmethylene. (Alk**) is preferably C2-C6-alkylene, more preferably C2-C4-alkylene and in particular ethylene. Q1 is preferably a radical R14 of formula (10) or a radical of formulae (9b) or (9c), in particular a radical of formula (9c).
Especially preferred radicals xe2x80x94Q1 correspond to formula 
A suitable moiety [Bxe2x80x3xe2x80x94Q] in formula (5) corresponds, for example, to formula 
wherein R5xe2x80x3 is hydrogen or C1-C4-alkyl, preferably hydrogen or methyl, and for Q1, X, R11 and t each the above given meanings and preferences apply. An especially preferred moiety [Bxe2x80x3xe2x80x94Q] of formula (5) corresponds to the formula (6c) above, wherein t is 1, R11 is a radical of the formula (8a) above, preferably a radical xe2x80x94CON(C1-C2-alkyl)-CH2xe2x80x94CH2xe2x80x94 or xe2x80x94CONHxe2x80x94CH2xe2x80x94CH2xe2x80x94, X is xe2x80x94Oxe2x80x94, and Q1 is a radical 
The total of (p+q) is, for example, an integer from 2 to 150, more preferably from 5 to 100, even more preferably from 5 to 75 and particularly preferably from 10 to 50. u is preferably a number from 1 to 3, and especially from 1 to 2. In one preferred embodiment of the invention u is a number from 1 to 2, q is 0, and p is an integer from 1 to 149, preferably from 3 to 99, more preferably from 4 to 74 and particularly preferably from 9 to 49. In another preferred embodiment of the invention u is a number from 1 to 2 , p and q are each independently an integer of xe2x89xa71 and the sum of (p+q) is an integer from 2 to 149, preferably from 3 to 99, more preferably from 4 to 74 and especially from 9 to 49.
The hydrophilic blocks, for example, of formula (5) have an weight average molecular weight of, for example, 200 to 20000, preferably 250 to 12500, more preferably from 350 to 5000, and in particular 500 to 2500.
The variable n in formula (1) is for example an integer from 1 to 20, preferably from 1 to 10, more preferably from 2 to 8 and even more preferably from 2 to 6. One especially preferred embodiment of the invention relates to block copolymers of formula (1), wherein n is the number 2. Another embodiment relates to block copolymers of formula (1), wherein n is an integer from 3 to 8 and in particular 4 to 6.
The structure of the crosslinkable copolymers of the invention may vary within wide limits. They may thus consist in one embodiment of one segment A and one segment -[L-(alk)-S-(oligomer)-(Q)m] only (diblock copolymers), or of one segment A and two segments -(alk)-S-(oligomer)-(Q)m linked to its termini by the linking group L (triblock copolymers, or may have a comb-type structure wherein several fragments -[L-(alk)-S-(oligomer)-(Q)m] are pendent from one segment A (comb-block copolymers), wherein A, L, (alk), (oligomer) and (Q)m each have the above-given meaning.
Formulae (3), (4) and (5) are to be understood as a statistic description of the respective compounds and radicals, that is to say the orientation and sequence of the units are not fixed in anyway by said formulae. In addition, the value of m or u in formulae (1) and (1a) is a statistically one which indicates that for a given number of n segments -[L-(alk)-S-(oligomer)] within a copolymer of formula (1) each of said segments statistically comprises m or u units Q or Q1.
One group of preferred amphiphilic block copolymers of the invention are triblock copolymers of formula 
wherein R5xe2x80x2 independently has the meaning of R5, R6xe2x80x2 independently has the meaning of R6, n is 2, and for A, L, (alk), R5, R5xe2x80x3, R6, R6xe2x80x2, R11, X, Q1, T, p, q, u and t each the above given meanings and preferences apply.
The block copolymers of formula (1) may be prepared by methods known per se. For example, in a first step there is provided a compound of formula 
wherein A, L, (alk), (oligomer), R11, X, n und t each have the above given meaning and m1 is an integer of xe2x89xa71, for example an integer from 1 to 150, which is then reacted with about (nxe2x80xa2m) molar equivalents of, for example, a compound of formula 
wherein Hal is halogen, in particular bromine or chlorine, R14xe2x80x2 has the meaning of R14 reduced by the carbonyl group, and R14, (Alk*) and (Alk**) are each as defined above.
Preferably, the oligomer portion of the compound of formula (11) is a homopolymer or copolymer derived from one or two hydrophilic ethylenically unsaturated monomers, wherein at least one of said monomers comprises a functional group that is coreactive with a carboxylic acid halide, carboxylic acid anhydride, epoxy, lactone, aziactone or isocyanato group, and which is endcapped in part with a compound, for example, of formula (12a), (12b), (12c), (12d) or (12e).
The reactions of a compound of formula (12a)-(12e) having a carboxylic acid halide group, carboxylic acid anhydride group, epoxy group, azlactone group or isocyanato group with an thiol, amino or hydroxy compound of formula (11) are well-known in the art and may be carried out as desribed in textbooks of organic chemistry.
For example, the reaction of the carboxylic acid halide of formula (12a) with a compound of formula (11) can be carried out under the conditions that are customary for ester, thioester, or amide formation, for example at temperatures of, for example, from xe2x88x9240 to 80xc2x0 C., preferably from 0 to 50xc2x0 C. and most preferably from 0 to 25xc2x0 C., in a dipolar aprotic solvent, e.g. tetrahydrofuran, dioxane, DMSO or an aprotic solvent as mentioned below, or in a mixture of water and one of the mentioned solvents, in the presence of a base, e.g. an alkali metal hydroxide, and, where applicable, in the presence of a stabiliser. Suitable stabilisers are, for example, 2,6-dialkylphenols, hydroquinone derivatives, e.g. hydroquinone or hydroquinone monoalkyl ethers, or N-oxides, e.g. 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-yl. The reaction times may vary within wide limits, a period of, for example, from 30 minutes to 12 hours, preferably from 1 to 6 hours and especially from 2 to 3 hours, generally having been found practicable.
The reaction of a carboxylic acid anhydride or epoxide of formula (12b) or (12c) with a compound of formula (11) may be carried out as described in organic textbooks, for example in an acidic or in a basic medium.
The reaction of an azlactone of formula (12d) with a compound of formula (11) may be carried out at elevated temperature, for example at about 50 to 75xc2x0 C., in a suitable organic solvent, for example an aprotic polar solvent such as DMF, DMSO, dioxane and the like, optionally in the presence of a catalyst, for example in the presence of a tertiary amine such as triethyl amine or an organotin salt such as dibutyltin dilaurate, or in particular in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
The reaction of a compound of formula (12e) with a compound of formula (11) can be carried out under the conditions that are customary for the formation of urethanes or ureas. In case of urethane formation it is advantageously to perform the reaction in an inert solvent. Amines of the formula (11) may be reacted with the isocyanate of formula (12e) also in an aqueous medium.
Suitable inert solvents for the reaction of a compound of formula (11) with a compound of formula (12e) are aprotic, preferably polar, solvents, for example hydrocarbons (petroleum ether, methylcyclohexane, benzene, toluene, xylene), halogenated hydrocarbons (chloroform, methylene chloride, trichloroethane, tetrachloroethane, chlorobenzene), ethers (diethyl ether, dibutyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, dioxane), ketones (acetone, dibutyl ketone, methyl ethyl ketone, methyl isobutyl ketone), carboxylic acid esters and lactones (ethyl acetate, butyrolactone, valerolactone), alkylated carboxylic acid amides (N,N-dimethylacetamide, N-methylpyrrolidone), nitriles (acetonitrile), sulfones and sulfoxides (dimethyl sulfoxide, tetramethylenesulfone). Polar solvents are preferably used. The reaction temperature may be, for example, from xe2x88x9240 to 200xc2x0 C. When catalysts are used, the temperatures may advantageously be in the range of from 0 to 50xc2x0 C., preferably at room temperature. Suitable catalysts are, for example, metal salts, such as ferric chloride or alkali metal salts of carboxylic acids, tertiary amines, for example (C1-C6alkyl)3N (tri-ethylamine, tri-n-butylamine), N-methylpyrrolidine, N-methylmorpholine, N,N-dimethylpiperidine, pyridine and 1,4-diaza-bicyclooctane. Tin salts have been found to be especially effective, especially alkyltin salts of carboxylic acids, for example dibutyltin dilaurate and tin dioctoate. The isolation and purification of the compounds prepared is carried out according to known methods, for example by means of extraction, crystallisation, recrystallisation or chromatographic purification methods.
The compounds of the formula (12a), (12b), (12c), (12d) and (12e) are known compounds which are commercially available or may be prepared according to known methods.
The compounds of formula (11) are novel and represent a further object of the invention. They may be prepared by methods known per se. For example the block copolymers of formula (1) having a linking group of formula of formula (2a) or (2b) may be prepared by reacting in any order a compound of formula
Axe2x80x94(X1H)nxe2x80x83xe2x80x83(13),
about n molar equivalents of a compound of formula
X*xe2x80x94Rxe2x80x94X*xe2x80x83xe2x80x83(14),
and about molar equivalents of a compound of formula 
wherein X* is a group xe2x80x94Nxe2x95x90Cxe2x95x90O or carboxy or a suitable derivative thereof, for example a group xe2x80x94C(O)OH, xe2x80x94C(O)OR20 or xe2x80x94C(O)xe2x80x94OHal wherein R20 is, for example, C1-C4-alkyl, phenyl or benzyl and Hal is halogen, in particular bromine or chlorine, and A, R, R11 X, X1, X2, (alk), (oligomer), n, m1 and t are each as defined above.
For example, the compound of formula (13) may be first reacted with about one molar equivalent of a compound of formula (14), and the intermediate obtained is then reacted with the compound of formula (15). Another synthetic route comprises first reacting a compound of formula (15) with a compound of formula (14), and the intermediate obtained is then reacted with a compound of formula (13). The reactions can be carried out under the conditions that are customary for ester, thioester, amide, urethane or urea formation, for example as outlined above.
The amphiphilic block copolymers of the invention wherein L is a linking group of formulae (2c) or (2d) may be prepared , for example, by reacting a compound of the formula
Axe2x80x94(X**)nxe2x80x83xe2x80x83(13a)
with about n molar equivalents of a compound of the above formula (15), or by reacting a compound of the above formula (13) with about n molar equivalents of a compound of formula 
wherein X** is carboxy or a suitable derivative thereof, for example a group xe2x80x94C(O)OH, xe2x80x94C(O)OR20 or xe2x80x94C(O)xe2x80x94OHal, and R, R11, R20 X, Hal, (alk), (oligomer), n, m1 and t each have the above-mentioned meaning.
The reaction of the components of formulae (13a) and (15) or (13) and (15a), respectively, can be carried out under the conditions that are customary for ester, thioester or amide formation, for example as outlined above.
The amphiphilic block copolymers of the invention wherein L is a linking group of formulae (2e) may be prepared, for example, by reacting a compound each of the formula (13) and (15) with phosgene.
The compounds of formulae (13), (13a) and (14) are known or may be obtained according to methods known in the art. Likewise, the hydrophilic telomers of formula (15) or (15a) may be prepared according to known processes, for example, according to PCT application WO 92/09639, by copolymerizing one or more hydrophilic ethylenically unsaturated monomers in the presence of a functional chain transfer agent wherein at least one monomer of the copolymerization mixture is capable afterwards to fix a crosslinkable or polymerizable moiety Q.
The compounds of formula 
wherein X4 is xe2x80x94SH, xe2x80x94NHR1, carboxy or a carboxy derivative, for example a group xe2x80x94C(O)OH, xe2x80x94C(O)OR20 or xe2x80x94C(O)xe2x80x94OHal, wherein R1, R20 and Hal are as defined above, and is preferably xe2x80x94NH2 or xe2x80x94NH(C1-C2-alkyl), and for (alk), B, Bxe2x80x2, Bxe2x80x3, T, p, q, t, u, R11 and X each the above given meanings and preferences apply, are novel and represent a further object of the invention.
A process for the preparation of the preferred compounds of formula (15) or (15a) comprises copolymerizing a mixture comprising
p molar equivalents of a compound of formula 
q molar equivalents of a compound of formula 
u equivalents of a compound of formula 
in the presence of a chain transfer agent of formula
HXxe2x80x2-(alk)-SHxe2x80x83xe2x80x83(18)
and optionally in the presence of an initiator for radical polymerization, wherein Xxe2x80x2 has the meaning of xe2x80x94X2H or X** above, and R5, R5xe2x80x2, R5xe2x80x3, R6, R6xe2x80x2, R11, X and t each have the above given meaning.
Since the compounds of formulae (16) and (17) may be identical, a particularly preferred process for the preparation of the compounds of formula (15) or (15a) comprises homo- or copolymerizing (p+u) equivalents of a monomer of formula (17) and optionally q equivalents of a monomer of formula (16a).
The radical polymerization of the monomer mixture may be induced photochemically or preferably thermally. Suitable thermal polymerization initiators are known to the skilled artisan and comprise, for example peroxides, hydroperoxides, azo-bis(alkyl- or cycloalkylnitriles), persulfates, percarbonates or mixtures thereof. Examples are benzoylperoxide, tert.-butyl peroxide, di-tert.-butyl-diperoxyphthalate, tert.-butyl hydroperoxide, azo-bis(isobutyronitrile), 1,1-azodiisobutyramidine, 1,1xe2x80x2-azo-bis (1-cyclohexanecarbonitrile), 2,2xe2x80x2-azo-bis(2,4-dimethyl-valeronitrile) and the like. Examples of suitable chain transfer agents of formula (18) are cysteamine (usually introduced as hydrochloride) or thioglycolic acid. The polymerization is carried out conveniently in an aqueous medium, preferably in an acidic medium which has a pH of from 2 to 6 and preferably 3 to 5, such as aqueous acetic acid or deluted hydrochloric acid, at elevated temperature, for example at a temperature of from 25 to 100xc2x0 C. and preferably 40 to 80xc2x0 C. The resulting telomer mixtures may be worked up in conventional manner using for example extraction, precipitation, ultrafiltration and the like techniques.
The hydrophilic blocks -[L-(alk)-S-(oligomer)-(Q)m] of the block copolymers of the invention have an weight average molecular weight of, for example, from 200 to 20000, preferably from 250 to 12500, more preferably from 350 to 5000, and in particular from 500 to 2500.
The molecular weight of the copolymers of the formula (1) is, within wide limits, not critical. Preferably, however, the prepolymer has a weight average molecular weight of from approximately 1400 to 200000, preferably from 2000 to 100000 and more preferably from 2500 to 50000 and most preferably from 3000 to 25000.
The amphiphilic block copolymers formula (1) are prepolymers and are therefore crosslinkable, but uncrosslinked or, at least, substantially uncrosslinked; in addition, they are stable, that is to say spontaneous crosslinking as a result of homopolymerisation does not take place.
The prepolymers of formula (1) according to the invention are crosslinkable in a controlled and extremely effective manner, especially by photo-crosslinking.
The present invention further relates, therefore, to a polymer that can be obtained by photo-crosslinking of a prepolymer of formula (1), in the presence or, preferably, in the absence of an additional vinyl comonomer. These crosslinked polymers are water-insoluble.
In the photo-crosslinking, a photoinitiator capable of initiating free-radical crosslinking is suitably added. Examples thereof will be familiar to the person skilled in the art, suitable photoinitiators that may specifically be mentioned being benzoin methyl ether, 1-hydroxycyclohexylphenyl ketone, Darocure 1173 or Irgacure types. The crosslinking can then be brought about by actinic radiation, e.g. UV light, or ionising radiation, e.g. gamma rays or X-rays. The amount of photoinitiator may be selected within wide limits, an amount of up to 0.05 g/g of polymer and especially of up to 0.003 g/g of polymer having proved beneficial.
The crosslinkable copolymer of formula (1) is introduced into the crosslinking process preferably in pure form, particularly substantially free from undesired constituents, such as, for example, free from monomeric, oligomeric or polymeric starting compounds used for the preparation of the prepolymer, and/or free from secondary products formed during the preparation of the prepolymer. Said prepolymers in pure form are obtained advantageously by previously purifying them in a manner known per se, for example by precipitation with a suitable solvent, filtration and washing, extraction in a suitable solvent, dialysis, reverse osmoses (RO) or ultrafiltration, reverse osmoses and ultrafiltration being especially preferred.
The preferred purification processes for the prepolymers of the invention, reverse osmoses and ultrafiltration, can be carried out in a manner known per se. It is possible for the ultrafiltration and reverse osmoses to be carried out repeatedly, for example from two to ten times. Alternatively, the ultrafiltration and reverse osmoses can be carried out continuously until the selected degree of purity is attained. The selected degree of purity can in principle be as high as desired.
The copolymers of formula (1) may be crosslinked, for example, in form of a solution or a mesophase.
One embodiment of the invention relates to the photo-polymerisation of the block copolymers of the invention in solution, preferably in one or more different organic solvents. Suitable solvents are in principle all solvents that dissolve the polymers according to the invention and an optional vinyl comonomer which may be additionally used, e.g. alcohols, such as C1-C6- alkanols, e.g. n- or iso-propanol, ethanol or methanol, glycols such as ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, carboxylic acid amides, such as dimethylformamide, or dimethyl sulfoxide, and mixtures of suitable solvents, e.g. mixtures of water with an alcohol, e.g. a water/propanol, water/ethanol or a water/methanol mixture, or mixtures of water with a glycol.
According to this embodiment of the invention, the photo-crosslinking is preferably effected from a solution comprising (i) one or more prepolymers according to the invention which can be obtained as a result of the preferred purification step, ultrafiltration, (ii) one or more solvents selected from the group consisting of a C1-C6- alkanol, a glycol, a carboxylic acid amide, dimethyl sulfoxide and water, and optionally (iii) an additional vinyl comonomer. For example, photo-crosslinking of the prepolymers is carried out in ethanol or n- or iso-propanol.
The vinyl comonomer that can additionally be used according to the invention in the photo-crosslinking may be hydrophilic or hydrophobic or may be a mixture of a hydrophobic and a hydrophilic vinyl monomer. Suitable vinyl monomers include especially those which are customarily used in the manufacture of contact lenses. The expression xe2x80x9chydrophilic vinyl monomerxe2x80x9d is understood to mean a monomer that typically produces as homopolymer a polymer that is water-soluble or capable of absorbing at least 10% by weight water. Analogously, the expression xe2x80x9chydrophobic vinyl monomerxe2x80x9d is understood to mean a monomer that typically produces as homopolymer a polymer that is water-insoluble or capable of absorbing less than 10% by weight water.
The proportion of vinyl comonomers, if used, is preferably from 0.5 to 80 units per prepolymer of formula (1), especially from 1 to 30 units of vinyl comonomer per prepolymer unit of formula (1) and most preferably from 5 to 20 units per prepolymer of formula (1).
It is also preferred to use a hydrophobic vinyl comonomer or a mixture of a hydrophobic vinyl comonomer with a hydrophilic vinyl comonomer, the mixture containing at least 50% by weight of a hydrophobic vinyl comonomer. In that manner, the mechanical properties of the polymer can be improved without the water content being appreciably reduced. In principle, however, both conventional hydrophobic vinyl comonomers and conventional hydrophilic vinyl comonomers are suitable for copolymerisation with a prepolymer of formula (1).
Suitable hydrophobic vinyl comonomers include, without the following being an exhaustive list, C1-C18alkyl acrylates and methacrylates, C3-C18alkylacrylamides and -methacrylamides, acrylonitrile, methacrylonitrile, vinyl-C1-C18alkanoates, C2-C18alkenes, C2-C18haloalkenes, styrene, C1-C6alkylstyrene, vinyl alkyl ethers in which the alkyl moiety has from 1 to 6 carbon atoms, C2-C10perfluoroalkyl acrylates and methacrylates or correspondingly partially fluorinated acrylates and methacrylates, C3-C12perfluoroalkyl-ethyl-thiocarbonylaminoethyl acrylates and methacrylates, acryloxy- and methacryloxy-alkylsiloxanes, N-vinylcarbazole, C1-C12alkyl esters of maleic acid, fumaric acid, itaconic acid, mesaconic acid and the like. Preferred are, for example, C1-C4alkyl esters of vinylically unsaturated carboxylic acids having from 3 to 5 carbon atoms or vinyl esters of carboxylic acids having up to 5 carbon atoms.
Examples of suitable hydrophobic vinyl comonomers include methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, methyl meth-acrylate, ethyl methacrylate, propyl methacrylate, vinyl acetate, vinyl propionate, vinyl butyrate, vinyl valerate, styrene, chloroprene, vinyl chloride, vinylidene chloride, acrylonitrile, 1-butene, butadiene, methacrylonitrile, vinyltoluene, vinyl ethyl ether, perfluorohexylethylthio-carbonylaminoethyl methacrylate, isobornyl methacrylate, trifluoroethyl methacrylate, hexa-fluoroisopropyl methacrylate, hexafluorobutyl methacrylate, tris-trimethylsilyloxy-silyl-propyl methacrylate, 3-methacryloxypropylpentamethyldisiloxane and bis(methacryloxypropyl)-tetramethyidisiloxane.
Suitable hydrophilic vinyl comonomers include, without the following being an exhaustive list, hydroxy-substituted lower alkyl acrylates and methacrylates, acrylamide, methacrylamide, lower alkylacrylamide and -methacrylamide, ethoxylated acrylates and methacrylates, hydroxy-substituted lower alkylacrylamides and methacrylamides, hydroxy-substituted lower alkyl vinyl ethers, sodium ethylenesulfonate, sodium styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid, N-vinylpyrrole, N-vinylsuccinimide, N-vinylpyrrolidone, 2- or 4-vinylpyridine, acrylic acid, methacrylic acid, amino- (the term xe2x80x9caminoxe2x80x9d also including quaternary ammonium), mono-lower alkylamino- or di-lower alkylamino-lower alkyl acrylates and methacrylates, allyl alcohol and the like. Preferred are, for example, hydroxy-substituted C2-C4alkyl (meth)acrylates, five- to seven-membered N-vinyl lactams, N,N-di-C1-C4alkyl(meth)-acrylamides and vinylically unsaturated carboxylic acids having a total of from 3 to 5 carbon atoms.
Examples of suitable hydrophilic vinyl comonomers include hydroxyethyl methacrylate, hydroxyethyl acrylate, acrylamide, methacrylamide, dimethylacrylamide, allyl alcohol, vinyl-pyridine, vinylpyrrolidine, glycerol methacrylate, N-(1,1-dimethyl-3-oxobutyl)-acrylamide and the like.
Preferred hydrophobic vinyl comonomers are methyl methacrylate and vinyl acetate. Preferred hydrophilic vinyl comonomers are 2-hydroxyethyl methacylate, N-vinylpyrrolidone and acrylamide. Most preferably, the crosslinking of the copolymers of formula (1) is carried out in the absence of a vinylic comonomer.
According to another embodiment of the invention, the copolymers of formula (1) are previously converted into an aqueous mesophase which is at least partly bicontinuous, and the aqueous mesophase is then subjected to photocrosslinking. A suitable process for producing an aqueous mesophase composition and its crosslinking in an ophthalmic mould is disclosed in PCT application WO 99/12059, which application is herein incorporated by reference. A mesophase of a block copolymer of the invention may be prepared, for example, by simply admixing suitable amounts of (i) a prepolymer of formula (1), (ii) an aqueous solution which may comprise, in addition to water, for example a water-miscible solvent and/or salts, and (iii) optionally further components such as a photoinitiator, a surfactant a hydrophobic or hydrophilic comonomer as mentioned before, or a pharmaceutical effective agent, for example a protein, enzyme, vitamin, disinfectant, bactericide or the like, in any order at a temperature of, for example, 0 to 100xc2x0 C., preferably 10 to 50xc2x0 C., and more preferably 15 to 40xc2x0 C. The mesophases may form spontaneously or upon stirring and/or standing for a suitable period. For example, the components that make up the mesophase are mixed for about 1 minute to 1 week, preferably for 30 minutes to 5 days and most preferably 2 hours to 3 days, in order to form a mesophase which is ready for being further processed according to the invention.
Mesophases of a block copolymer of the invention comprise, for example, from 10 to 100 percent by weight of block copolymer(s) of formula (1), from about 0 to about 90 percent by weight of aqueous solution and from 0 to 40 percent by weight of further components. Preferably, the bicontinuous mesophases of a block copolymer of the invention comprise from about 30 to about 85 percent by weight of prepolymer(s) of formula (1), from about 15 to about 70 percent by weight of aqueous solution and from 0 to 10 percent by weight of further components. Particularly preferred mesophases comprise from 30 to 75 percent by weight of prepolymer(s) of formula (1) and from 25 to 70 percent by weight of aqueous solution.
The solutions or mesophases comprising a block copolymer of formula (1) may be processed in a manner known per se to form mouldings, especially contact lenses, for example by carrying out the photo-crosslinking of the prepolymers of the invention in a suitable mould, in particular a contact lens mould. For example, the solution or mesophase is introduced into an opthalmic mould in a manner known per se, such as, especially, by conventional metering in, for example by dropwise introduction or by extrusion. Suitable moulds are generally customary contact lens moulds as known in the state of the art. Thus, the contact lenses according to the invention can be manufactured, for example, in a manner known per se, for example in a conventional xe2x80x9cspin-casting mouldxe2x80x9d, as described, for example, in U.S. Pat. No. 3,408,429, or by the so-called Full-Mould process in a static mould, as described, for example, in U.S. Pat. No. 4,347,198. Appropriate moulds are made, for example, from polypropylene. Quartz, sapphire glass and metals, for example, are suitable materials for re-usable moulds.
The crosslinking can be triggered in the mould, for example by actinic radiation, such as, for example, UV light, or by ionising radiation, such as, for example, gamma radiation, electron radiation or X radiation. The crosslinking can where appropriate also be triggered thermally or electrochemically. Attention is drawn to the fact that the photocrosslinking can be carried out in a very short time, for example in xe2x89xa630 minutes, preferably xe2x89xa620 minutes, more preferably xe2x89xa65 minutes, even more preferably in xe2x89xa61 minute, especially in 10 to 60 seconds, especially preferably, as disclosed in the examples.
The opening of the mould such that the moulding can be removed from the mould can be carried out in a manner known per se.
The mouldings obtainable from the block copolymers of formula (1) are preferably at least partly bicontinuous, that is to say the mouldings have at least two partly bicontinuous phases, for example an oxygen-permeable and an ion-permeable phase, which are intermingled.
The invention further relates, therefore, to mouldings that comprise or, preferably, substantially consist of a crosslinked block copolymer of formula (1). Further examples of mouldings of the invention, apart from contact lenses, are biomedical or special ophthalmic mouldings, e.g. intraocular lenses, artificial cornea, eye dressings, mouldings for use in surgery, such as heart valves, artificial arteries or the like, and films or membranes, e.g. membranes for controlling diffusion, photo-structurable films for information storage, or photoresist materials, e.g. membranes or mouldings for etch resists or screen print resists.
If the moulding manufactured according to the invention is a contact lens and the latter has been manufactured from a previously purified prepolymer using an organic solvent such as an alcohol or an aqueous solution comprising an alcohol or the like, then it is normally unnecessary for the removal of the moulding to be followed by purification steps, e.g. extraction, because the prepolymers used do not contain any undesired low-molecular-weight constituents; consequently, the crosslinked product also is free or substantially free of such constituents and subsequent extraction can be dispensed with. The contact lens can accordingly be converted into a ready-for-use contact lens directly in conventional manner by hydration. Suitable forms of hydration capable of producing ready-for-use contact lenses with a wide variety of water contents are known to the person skilled in the art. The contact lens is swelled, for example, in water, in an aqueous salt solution, especially in an aqueous salt solution having an osmolarity of approximately from 200 to 450 milliosmol in 1000 ml (unit: mosm/l), preferably approximately from 250 to 350 mosm/l and especially approximately 300 mosm/l, or in a mixture of water or an aqueous salt solution with a physiologically tolerable polar organic solvent, for example glycerol. Swelling of the prepolymer in water or in aqueous salt solutions is preferred.
The aqueous salt solutions used for the hydration are advantageously solutions of physiologically tolerable salts, such as buffer salts customary in the field of contact lens care, e.g. phosphate salts, or isotonising agents customary in the field of contact lens care, such as, especially, alkali metal halides, e.g. sodium chloride, or solutions of mixtures thereof. An example of an especially suitable salt solution is a synthetic, preferably buffered, lachrymal fluid that has been matched to natural lachrymal fluid with regard to pH value and osmolarity, e.g. an unbuffered or preferably buffered, for example phosphate buffer-buffered, sodium chloride solution the osmolarity and pH value of which correspond to the osmolarity and pH value of human lachrymal fluid.
The hydration fluids defined above are preferably pure, that is to say free or substantially free of undesired constituents. Most preferably, the hydration fluid is pure water or a synthetic lachrymal fluid as described above.
If the moulding manufactured according to the invention is a contact lens and the latter has been manufactured from an aqueous mesophase of a previously purified prepolymer of the invention, the crosslinked product also will not contain any troublesome impurities. There is normally no need, therefore, for subsequent extraction. Since the crosslinking is carried out in an aqueous medium, there is also no need for subsequent hydration. In accordance with an advantageous embodiment, therefore, the contact lenses obtainable by this process are distinguished by the fact that they are suitable for use as intended without extraction or hydration. The expression xe2x80x9cuse as intendedxe2x80x9d is understood in this context to mean especially that the contact lenses can be inserted into the human eye.
The copolymers of the invention are especially suitable for the manufacture of mass-produced articles, such as, for example, contact lenses that are worn for a short time, for example for a month, a week or just one day, and are then replaced by new lenses. This is in particular because contact lenses prepared from a mesophase of the copolymers can be used for their intended use without subsequent treatment steps, such as extraction or hydration.
In addition, the contact lenses obtainable according to the invention have a range of unusual and extremely advantageous properties and are therefore suited to extended periods of wear (true extended wear, i.e., seven days or more). Among these properties are, for example, their excellent compatibility with the human cornea and with tear fluid, if necessary after suitable surface treatment (e.g. coating), which is based on a balanced ratio between water content, oxygen permeability, ion permeability and mechanical and absorptive properties. This results in high comfort and the absence of irritation and allergenic effects. Owing to their favourable permeability properties with respect to gases (CO2 and O2), various salts, nutrients, water and diverse other components of tear fluid, the contact lenses prepared according to the process of the invention have no effect, or virtually no effect, on the natural metabolic processes in the cornea. Furthermore, the contact lenses obtainable according to the process are optical clear and transparent, have a high shelf life and good mechanical properties, for example concerning the modulus of elasticity, elongation at break or dimensional stability.
All of the advantages mentioned above apply, of course, not only to contact lenses but also to other mouldings of the invention. The sum of the various advantageous aspects in the manufacture of the mouldings of the invention results in the mouldings of the invention being especially suitable as mass-produced articles, such as, for example, contact lenses that are worn for a short period and then replaced by new lenses.
In the Examples which follow, amounts are by weight, unless specified otherwise, and temperatures are given in degrees Celsius.
Preparation of Telomers of Formula (15)